West M A, Billiar T R, Curran R D, Hyland B J, Simmons R L
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
Gastroenterology. 1989 Jun;96(6):1572-82. doi: 10.1016/0016-5085(89)90529-5.
Kupffer cell control of hepatocyte protein synthesis may be an important mechanism involved in the regulation of normal liver function and may be one mechanism responsible for the alterations in liver function seen during sepsis. The present series of in vitro experiments compare the response to various inflammatory stimuli of hepatocytes cocultured with Kupffer cells with that of hepatocytes cultured alone. In the absence of inflammatory stimuli, Kupffer cells stimulated hepatocyte protein synthesis. Lipopolysaccharide or gentamicin-killed Escherichia coli triggered Kupffer cell-mediated inhibition of cocultured hepatocyte protein synthesis but had no effect on protein synthesis of hepatocytes cultured alone. Phorbol myristate acetate, muramyl dipeptide, and calcium ionophore had no effect on hepatocytes cultured alone but resulted in a loss of Kupffer cell-mediated stimulation of cocultured hepatocyte protein synthesis without inhibition. Addition of dexamethasone to cocultures prevented the Kupffer cell-mediated inhibition of hepatocyte protein synthesis triggered by lipopolysaccharide, but did not block Kupffer cell-mediated stimulation in the absence of lipopolysaccharide. The data suggest that Kupffer cells can stimulate and inhibit hepatocyte protein synthesis by independent mechanisms. Kupffer cells may be important regulators of hepatocellular function in health and disease.
库普弗细胞对肝细胞蛋白质合成的调控可能是参与正常肝功能调节的重要机制，也可能是脓毒症期间所见肝功能改变的原因之一。本系列体外实验比较了与库普弗细胞共培养的肝细胞和单独培养的肝细胞对各种炎症刺激的反应。在无炎症刺激的情况下，库普弗细胞可刺激肝细胞蛋白质合成。脂多糖或庆大霉素灭活的大肠杆菌可引发库普弗细胞介导的共培养肝细胞蛋白质合成抑制，但对单独培养的肝细胞蛋白质合成无影响。佛波酯、胞壁酰二肽和钙离子载体对单独培养的肝细胞无影响，但会导致库普弗细胞介导的共培养肝细胞蛋白质合成刺激作用丧失，而无抑制作用。在共培养体系中添加地塞米松可防止脂多糖引发的库普弗细胞介导的肝细胞蛋白质合成抑制，但在无脂多糖时并不阻断库普弗细胞介导的刺激作用。数据表明，库普弗细胞可通过独立机制刺激和抑制肝细胞蛋白质合成。库普弗细胞可能是健康和疾病状态下肝细胞功能的重要调节因子。
